tbuckley/cabot-search huggingface dataset:
LncRNA Osilr9 coordinates promoter DNA demethylation and the intrachromosomal loop structure required for maintaining stem cell pluripotency
Authors: Yanbo Zhu, Zi Yan, Changhao Fu, Xue Wen, Lin Jia, Lei Zhou, Zhonghua Du, Cong Wang, Yichen Wang, Jingcheng Chen, Yuanyuan Nie, Wenjun Wang, Jiuwei Cui, Guixia Wang, Andrew R. Hoffman, Ji-Fan Hu, Wei Li
Journal: Molecular Therapy (2022)

Nuclear reprogramming of somatic cells into a pluripotent status has the potential to create patient-specific induced pluripotent stem cells for regenerative medicine. Currently, however, the epigenetic mechanisms underlying this pluripotent reprogramming are poorly understood. To delineate this epigenetic regulatory network, we utilized a chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to identify long noncoding RNAs (lncRNAs) embedded in the 3-dimensional intrachromosomal architecture of stem cell core factor genes. By combining CRIST-seq and RNA sequencing, we identified Oct4-Sox2 interacting lncRNA 9 (Osilr9) as a pluripotency-associated lncRNA. Osilr9 expression was associated with the status of stem cell pluripotency in reprogramming. Using short hairpin RNA (shRNA) knockdown, we showed that this lncRNA was required for the optimal maintenance of stem cell pluripotency. Overexpression of Osilr9 induced robust activation of endogenous stem cell core factor genes in fibroblasts. Osilr9 participated in the formation of the intrachromosomal looping required for the maintenance of pluripotency. After binding to the Oct4 promoter, Osilr9 recruited the DNA demethylase ten-eleven translocation 1, leading to promoter demethylation. These data demonstrate that Osilr9 is a critical chromatin epigenetic modulator that coordinates the promoter activity of core stem cell factor genes, highlighting the critical role of pluripotency-associated lncRNAs in stem cell pluripotency and reprogramming.
Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma
Authors: Gajanan Kendre, Karthikeyan Murugesan, Tilman Brummer, Oreste Segatto, Anna Saborowski, Arndt Vogel
Journal: Journal of Hepatology (2022)

In recent years, intrahepatic cholangiocarcinoma (iCCA) has evolved as a "role model" for precision oncology in gastrointestinal cancers. However, its rarity, paired with its genomic heterogeneity, challenges the development and evolution of targeted therapies. Interrogating large datasets drives better understanding of the characteristics of molecular subgroups of rare cancers and enables the identification of genomic patterns that remain unrecognized in smaller cohorts.We performed a retrospective analysis of 6,130 patients diagnosed with iCCA from the FoundationCORE database who received diagnostic panel sequencing on the FoundationOne platform. Short variants/fusion-rearrangements and copy number alterations in >300 tumor-associated genes were evaluated, and the tumor mutational burden (TMB) as well as the microsatellite instability (MSI) status were available for the majority of the cohort.We provide a highly representative cartography of the genomic landscape of iCCA and outline the co-mutational spectra of seven therapeutically relevant oncogenic driver genes: IDH1/2, FGFR2, ERBB2, BRAF, MDM2, BRCA1/2, MET and KRASG12C. We observed a negative selection of RTK/RAS/ERK pathway co-alterations, and an enrichment of epigenetic modifiers such as ARID1A and BAP1 in patients with IDH1/2 and FGFR2 alterations. RNF43 as well as KMT2D occurred with high frequency in MSIhigh and TMBhigh tumors.Detailed knowledge of the most prevalent genomic constellations is key to the development of effective treatment strategies for iCCA. Our study provides a valuable resource that could be used to assess the feasibility of clinical trials and subgroup analyses, spurs the development of translationally relevant preclinical models, and serves as a knowledge base to predict potential mechanisms of resistance to targeted therapies in genomically defined subgroups.Due to the high frequency of targetable alterations, molecular diagnostics is recommended in patients with biliary tract cancers, and especially in those with iCCA. The identification of an actionable lesion, however, does not guarantee therapeutic success, and the co-mutational spectrum may act as a critical modifier of drug response. Using a large dataset of comprehensive panel sequencing results from 6,130 patients with iCCA, we provide a detailed analysis of the co-mutational spectrum of the most frequent druggable genetic alterations, which is meant to serve as a reference to establish genetically relevant preclinical models, develop hypothesis-driven combination therapies and identify recurrent genetic profiles.
Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study
Authors: Neeraj Narula, Emily C L Wong, Cara Pray, John K Marshall, Sumathy Rangarajan, Shofiqul Islam, Ahmad Bahonar, Khalid F Alhabib, Anna Kontsevaya, Farnaza Ariffin, Homer U Co, Wadeia Al Sharief, Andrzej Szuba, Andreas Wielgosz, Maria Luz Diaz, Rita Yusuf, Lanthé Kruger, Biju Soman, Yang Li, Chuangshi Wang, Lu Yin, Erkin Mirrakhimov, Fernando Lanas, Kairat Davletov, Annika Rosengren, Patricio Lopez-Jaramillo, Rasha Khatib, Aytekin Oguz, Romaina Iqbal, Karen Yeates, Álvaro Avezum, Walter Reinisch, Paul Moayyedi, Salim Yusuf
Journal: Clinical Gastroenterology and Hepatology (2022)
Enforced expression of Runx3 improved CAR-T cell potency in solid tumor via enhancing resistance to activation-induced cell death
Authors: Yi Wang, Honghong Zhang, Guoxiu Du, Hong Luo, Jingwen Su, Yansha Sun, Min Zhou, Bizhi Shi, Henry Q.X. Li, Hua Jiang, Zonghai Li
Journal: Molecular Therapy (2022)
Annotating TSSs in Multiple Cell Types Based on DNA Sequence and RNA-Seq Data via DeeReCT-TSS
Authors: Juexiao Zhou, Bin Zhang, Haoyang Li, Longxi Zhou, Zhongxiao Li, Yongkang Long, Wenkai Han, Mengran Wang, Huanhuan Cui, Jingjing Li, Wei Chen, Xin Gao
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract The accurate annotation of transcription start sites (TSSs) and their usage are critical for the mechanistic understanding of gene regulation in different biological contexts. To fulfill this, specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner, and various computational tools have also been developed for in silico prediction of TSSs solely based on genomic sequences. Most of these computational tools cast the problem as a binary classification task on a balanced dataset, thus resulting in drastic false positive predictions when applied on the genome scale. Here, we present DeeReCT-TSS, a deep learning-based method that is capable of identifying TSSs across the whole genome based on both DNA sequence and conventional RNA sequencing data. We show that by effectively incorporating these two sources of information, DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types. Furthermore, we develop a meta-learning-based extension for simultaneous TSS annotations on 10 cell types, which enables the identification of cell type-specific TSSs. Finally, we demonstrate the high precision of DeeReCT-TSS on two independent datasets by correlating our predicted TSSs with experimentally defined TSS chromatin states. The source code for DeeReCT-TSS is available at https://github.com/JoshuaChou2018/DeeReCT-TSS_release and https://ngdc.cncb.ac.cn/biocode/tools/BT007316.
Inflammatory and insulinemic dietary patterns and risk of endometrial cancer among US women
Authors: Andrea Romanos-Nanclares, Fred K Tabung, Jennifer A Sinnott, Britton Trabert, Immaculata De Vivo, Mary C Playdon, A Heather Eliassen
Journal: JNCI Journal of the National Cancer Institute (2022)

Although unopposed estrogen exposure is considered a major driver of endometrial carcinogenesis, chronic inflammation and insulin resistance and hyperinsulinemia are also major endometrial cancer risk factors. However, it is unclear whether diets with inflammatory or insulinemic potential are associated with risk of endometrial cancer.
Genomic discoveries unveil mechanistic insights in diabetes
Authors: Jose C. Florez
Journal: Cell Genomics (2022)

Two diabetes-related papers are featured in this issue of Cell Genomics. Gardner et al.1 focus on type 2 diabetes through exome sequencing, and Benaglio et al.2 employ a functional genomics approach to advance understanding in type 1 diabetes. In this preview, Jose Florez highlights their contribution toward clinical translation of genomics discoveries.
Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development
Authors: Xiaochen Wang, Qifeng He, Chuanli Zhou, Yueyuan Xu, Danhui Liu, Naoto Fujiwara, Naoto Kubota, Arielle Click, Polly Henderson, Janiece Vancil, Cesia Ammi Marquez, Ganesh Gunasekaran, Myron E. Schwartz, Parissa Tabrizian, Umut Sarpel, Maria Isabel Fiel, Yarui Diao, Beicheng Sun, Yujin Hoshida, Shuang Liang, Zhenyu Zhong
Journal: Immunity (2022)
Multiple introductions and recombination events underlie the emergence of a hyper-transmissible Cryptosporidium hominis subtype in the USA
Authors: Wanyi Huang, Yaqiong Guo, Colleen Lysen, Yuanfei Wang, Kevin Tang, Matthew H. Seabolt, Fengkun Yang, Elizabeth Cebelinski, Olga Gonzalez-Moreno, Tianyi Hou, Chengyi Chen, Ming Chen, Muchun Wan, Na Li, Michele C. Hlavsa, Dawn M. Roellig, Yaoyu Feng, Lihua Xiao
Journal: Cell Host & Microbe (2022)
Evaluation of editors’ abilities to predict the citation potential of research manuscripts submitted to <i>The BMJ</i> : a cohort study
Authors: Sara Schroter, Wim E J Weber, Elizabeth Loder, Jack Wilkinson, Jamie J Kirkham
Journal: BMJ (2022)

To evaluate the ability of The BMJ editors to predict the number of times submitted research manuscripts will be cited.Cohort study.Manuscripts submitted to The BMJ, reviewed, and subsequently scheduled for discussion at a prepublication meeting between 27 August 2015 and 29 December 2016.10 BMJ research team editors.Reviewed manuscripts were rated independently by attending editors for citation potential in the year of first publication plus the next year: no citations, below average (<10 citations), average (10-17 citations), or high (>17 citations). Predicted citations were subsequently compared with actual citations extracted from Web of Science (WOS).Of 534 manuscripts reviewed, 505 were published as full length articles (219 in The BMJ) by end of 2019 and indexed in WOS, 22 were unpublished, and one abstract was withdrawn. Among the 505 manuscripts, the median (IQR [range]) number of citations in the year of publication plus the following year was 9 (4-17 [0-150]); 277 (55%) manuscripts were cited <10 times, 105 (21%) were cited 10-17 times, and 123 (24%) cited >17 times. Manuscripts accepted by The BMJ were cited more highly (median 12 (IQR 7-24) citations) than those rejected (median 7 (3-12) citations). For all 10 editors, predicted ratings tended to increase in line with actual citations, but with considerable variation within categories; nine failed to identify the correct citation category for >50% (range 31%-52%) of manuscripts, and κ ranged between 0.01 to 0.19 for agreement between predicted and actual categories. Editors more often rated papers that achieved high actual citation counts as having low citation potential than the reverse. Collectively, the mean percentage of editors predicting the correct citation category was 43%, and for 160 (32%) manuscripts at least 50% of editors predicted the right category.Editors weren't good at estimating the citation potential of manuscripts individually or as a group; there is no wisdom of the crowd when it comes to BMJ editors.
Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow
Authors: Takuya Koike, Kentaro Fujii, Kohei Kometani, Noah S. Butler, Kenji Funakoshi, Shinya Yari, Junichi Kikuta, Masaru Ishii, Tomohiro Kurosaki, Wataru Ise
Journal: The Journal of Experimental Medicine (2022)

The longevity of plasma cells is dependent on their ability to access and reside in so-called niches that are predominantly located in the bone marrow. Here, by employing a traceable method to label recently generated plasma cells, we showed that homeostatic plasma cells in the bone marrow and spleen were continuously replenished by newly generated B220hiMHC-IIhi populations that progressively differentiated into B220loMHC-IIlo long-lived plasma cell (LLPC) populations. We also found that, in the bone marrow, germinal center (GC)–independent and GC-dependent plasma cells decayed similarly upon NP-CGG engagement, and both entered the B220loMHC-IIlo LLPC pool. Compared with NP+B220hiMHC-IIhi plasma cells, NP+B220loMHC-IIlo cells were more immobilized in the bone marrow niches and showed better survival potential. Thus, our results suggest that the adhesion status of bone marrow plasma cells is dynamically altered during their differentiation and is associated with provision of survival signals.
Multicenter Randomized Trial of Intermittently Scanned Continuous Glucose Monitoring Versus Self-Monitoring of Blood Glucose in Individuals With Type 2 Diabetes and Recent-Onset Acute Myocardial Infarction: Results of the LIBERATES Trial
Authors: Ramzi A. Ajjan, Simon R. Heller, Colin C. Everett, Armando Vargas-Palacios, Ruchi Higham, Linda Sharples, Diana A. Gorog, Alice Rogers, Catherine Reynolds, Catherine Fernandez, Pedro Rodrigues, Thozhukat Sathyapalan, Robert F. Storey, Deborah D. Stocken
Journal: Diabetes Care (2022)

OBJECTIVE To analyze the impact of modern glucose-monitoring strategies on glycemic and patient-related outcomes in individuals with type 2 diabetes (T2D) and recent myocardial infarction (MI) and assess cost effectiveness. RESEARCH DESIGN AND METHODS LIBERATES was a multicenter two-arm randomized trial comparing self-monitoring of blood glucose (SMBG) with intermittently scanned continuous glucose monitoring (isCGM), also known as flash CGM, in individuals with T2D and recent MI, treated with insulin and/or a sulphonylurea before hospital admission. The primary outcome measure was time in range (TIR) (glucose 3.9–10 mmol/L/day) on days 76–90 post-randomization. Secondary and exploratory outcomes included time in hypoglycemia, hemoglobin A1c (HbA1c), clinical outcome, quality of life (QOL), and cost effectiveness. RESULTS Of 141 participants randomly assigned (median age 63 years; interquartile range 53, 70), 73% of whom were men, isCGM was associated with increased TIR by 17 min/day (95% credible interval −105 to +153 min/day), with 59% probability of benefit. Users of isCGM showed lower hypoglycemic exposure (&amp;lt;3.9 mmol/L) at days 76–90 (−80 min/day; 95% CI −118, −43), also evident at days 16–30 (−28 min/day; 95% CI −92, 2). Compared with baseline, HbA1c showed similar reductions of 7 mmol/mol at 3 months in both study arms. Combined glycemic emergencies and mortality occurred in four isCGM and seven SMBG study participants. QOL measures marginally favored isCGM, and the intervention proved to be cost effective. CONCLUSIONS Compared with SMBG, isCGM in T2D individuals with MI marginally increases TIR and significantly reduces hypoglycemic exposure while equally improving HbA1c, explaining its cost effectiveness. Studies are required to understand whether these glycemic differences translate into longer-term clinical benefit.
Public Access to Scientific Research Findings and Principles of Biomedical Research—A New Policy for the JAMA Network
Authors: Kirsten Bibbins-Domingo, Brian Shields, John Z. Ayanian, Robert O. Bonow, Neil M. Bressler, Dimitri Christakis, Mary L. Disis, S. Andrew Josephson, Melina R. Kibbe, Dost Öngür, Jay F. Piccirillo, Rita F. Redberg, Frederick P. Rivara, Kanade Shinkai, Thomas J. Easley
Journal: JAMA Neurology (2023)

Timely access to scientific research findings for the broadest possible audience is a principle on which sound science is based.Access to new findings helps other scientists adjust their hypotheses and open new lines of inquiry, thereby supporting and accelerating further discovery and innovation.For those who rely on newly generated evidence to develop policies and define practices that improve medicine and public health, rapid and equitable access is critical.The principle of broad access is a cornerstone of transparency, reinforces rigor and reproducibility, and ultimately, is critical to all stakeholders' trust in science.The biomedical ecosystem is complex-including scientists, research institutions, authors, journals, libraries, educators, general readers, clinicians, patients, regulators, policy makers, and funders.And while we likely agree on the importance of the ultimate outcome of public accessibility, in the debates about open access, data sharing, funder mandates, and the business models for publishing, it is easy to become untethered from these foundational principles.
Lung transplantation for end-stage cystic fibrosis before and after the availability of elexacaftor–tezacaftor–ivacaftor, Germany, 2012–2021
Authors: Felix C. Ringshausen, Annette Sauer-Heilborn, Tina Büttner, Anna-Maria Dittrich, Nicolaus Schwerk, Fabio Ius, Lutz Nährlich, Tobias Welte, Mark Greer
Journal: European Respiratory Journal (2022)

<b>This study observed a pronounced decline of CF-related lung transplants up to −83% in 2021 compared to the mean number in the period between 2012 and 2019, following the broad accessibility of elexacaftor-tezacaftor-ivacaftor in Germany in August 2020</b>https://bit.ly/3Pl7N9Y
Error in Table and Wording
Journal: JAMA Network Open (2022)

In the Research Letter titled "Full-time Work Rates of Physicians With Physician Spouses vs Nonphysician Spouses in Japan," 1 published November 14, 2022, there was an error in the number and percentage of male physicians with physician spouses who had 0 children listed in Table 1.In addition, "women" was changed to "female physicians" and "men" was changed to "male physicians" to clarify that participants reported sex rather than gender.This article has been corrected. 1
Alcohol Use Following Bariatric Surgery—A Cause for Concern and Call to Action
Authors: Jon C. Gould
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
<i>M</i><i>ycobacterium avium</i>complex genomics and transmission in a London hospital
Authors: Andries J. van Tonder, Huw C. Ellis, Colin P. Churchward, Kartik Kumar, Newara Ramadan, Susan Benson, Julian Parkhill, Miriam F. Moffatt, Michael R. Loebinger, William O.C. Cookson
Journal: European Respiratory Journal (2022)

Background Non-tuberculous mycobacteria (NTM) are environmental microorganisms and opportunistic pathogens in individuals with pre-existing lung conditions such as cystic fibrosis (CF) and non-CF bronchiectasis. While recent studies of Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, transmission of other NTM species is less well studied. Methods To investigate the potential for transmission of the Mycobacterium avium complex (MAC) we sequenced 996 isolates from 354 CF and non-CF patients at the Royal Brompton Hospital (London, UK; collected 2013–2016) and analysed them in a global context. Epidemiological links were identified from patient records. Previously published genomes were used to characterise global population structures. Results We identified putative transmission clusters in three MAC species, although few epidemiological links could be identified. For M. avium , lineages were largely limited to single countries, while for Mycobacterium chimaera , global transmission clusters previously associated with heater-cooler units (HCUs) were found. However, the immediate ancestor of the lineage causing the major HCU-associated outbreak was a lineage already circulating in patients. Conclusions CF and non-CF patients shared transmission chains, although the lack of epidemiological links suggested that most transmission is indirect and may involve environmental intermediates or asymptomatic carriage in the wider population.
Identification of two specific transcriptomic clusters of COVID-19 acute respiratory distress syndrome patients with different immune profiles and different outcomes
Authors: Yuichiro Shindo, Charles S. Dela Cruz, Martin Witzenrath
Journal: European Respiratory Journal (2022)

<b>Transcriptomic clustering of patients with ARDS due to COVID-19 identified different immune profiles and outcomes. This demonstrates heterogeneity among COVID-19 ARDS patients and may help to establish personalised therapies.</b>https://bit.ly/3h61sCj
Clinicians as Trusted Messengers—The “Secret Sauce” for Vaccine Confidence
Authors: Joanna G. Katzman, Ann S. Christiano
Journal: JAMA Network Open (2022)

Minjung Lee, PhD; Sujin Seo, BA; Syngjoo Choi, PhD; Jung Hyun Park, MA; Shinkyeong Kim, MPH; Young June Choe, MD; Eun Hwa Choi, MD; Geun-Yong Kwon, MD; Jee Yeon Shin, PhD; Sang-Yoon Choi, PhD; Mi Jin Jeong, MS; Hyunju Lee, MD; Myoungsoon You, PhD
Frailty as an Outcome Measurement Before and After Liver Transplant
Authors: Jenna N. Whitrock, Kristina H. K. Lemon, Shimul A. Shah
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal